Toxoplasmosis is caused by infection with the obligate intracellular parasite Toxoplasma gondii. Acute infection acquired after birth may be asymptomatic but is thought to result in the lifelong chronic persistence of cysts in the host's tissues. In both acute and chronic toxoplasmosis, the parasite is responsible for clinically evident disease, including lymphadenopathy, encephalitis, myocarditis, and pneumonitis. Congenital toxoplasmosis is an infection of newborns that results from the transplacental passage of parasites from an infected mother to the fetus. These infants may be asymptomatic at birth, but most later manifest a wide range of signs and symptoms, including chorioretinitis, strabismus, epilepsy, and psychomotor retardation. In immunocompetent individuals, toxoplasmosis can also present as acute disease (typically chorioretinitis) associated with food- or waterborne sources.
T. gondii is an intracellular coccidian that infects both birds and mammals. There are two distinct stages in the life cycle of T. gondii (Fig. 214-1). In the nonfeline stage, tissue cysts that contain bradyzoites or sporulated oocysts are ingested by an intermediate host (e.g., a human, mouse, sheep, pig, or bird). The cyst is rapidly digested by the acidic-pH gastric secretions. Bradyzoites or sporozoites are released, enter the small-intestinal epithelium, and transform into rapidly dividing tachyzoites. The tachyzoites can infect and replicate in all mammalian cells except red blood cells. Once attached to the host cell, the parasite penetrates the cell and forms a parasitophorous vacuole within which it divides. Parasite replication continues until the number of parasites within the cell approaches a critical mass and the cell ruptures, releasing parasites that infect adjoining cells. As a result of this process, an infected organ soon shows evidence of cytopathology. Most tachyzoites are eliminated by the host's humoral and cell-mediated immune responses. Tissue cysts containing many bradyzoites develop 7–10 days after systemic tachyzoite infection. These tissue cysts occur in various host organs but persist principally within the central nervous system (CNS) and muscle. The development of this chronic stage completes the nonfeline portion of the life cycle. Active infection in the immunocompromised host is most likely to be due to the spontaneous release of encysted parasites that undergo rapid transformation into tachyzoites within the CNS.
Life cycle of Toxoplasma gondii. The cat is the definitive host in which the sexual phase of the cycle is completed. Oocysts shed in cat feces can infect a wide range of animals, including birds, rodents, grazing domestic animals, and humans. The bradyzoites found in the muscle of food animals may infect humans who eat insufficiently cooked meat products, particularly lamb and pork. Although human disease can take many forms, congenital infection and encephalitis from reactivation of latent infection in the brains of immunosuppressed persons are the most important manifestations. CNS, central nervous system. (Courtesy of Dominique Buzoni-Gatel, Institut Pasteur, Paris; with permission.)
The principal (feline) stage in the life cycle takes place in the cat (the definitive host) and its prey. The parasite's sexual phase is defined by the formation of oocysts within the feline host. This enteroepithelial cycle begins with the ingestion of the bradyzoite tissue cysts and culminates (after several intermediate stages) in the production of gametes. Gamete fusion produces a zygote, which envelops itself in a rigid wall and is secreted in the feces as an unsporulated oocyst. After 2–3 days of exposure to air at ambient temperature, the noninfectious oocyst sporulates to produce eight sporozoite progeny. The sporulated oocyst can be ingested by an intermediate host, such as a person emptying a cat's litter box or a pig rummaging in a barnyard. It is in the intermediate host that T. gondii completes its life cycle. Sporulated oocysts, which are environmentally hardy and very infectious, are thought to be sources of waterborne outbreaks such as those reported in Victoria (British Columbia, Canada) and in South America.
T. gondii infects a wide range of mammals and birds. Its seroprevalence depends on the locale and the age of the population. Generally, hot arid climatic conditions are associated with a low prevalence of infection. In the United States and most European countries, the seroprevalence increases with age and exposure. For example, in the United States, 5–30% of individuals 10–19 years old and 10–67% of those >50 years old have serologic evidence of exposure. In Central America, France, Turkey, and Brazil, the seroprevalence is higher. Because of increased awareness of food-borne infections, the prevalence of seropositivity has decreased worldwide. There may be as many as 2100 cases of toxoplasmic encephalitis (TE) each year in the United States.
The principal source of human Toxoplasma infection remains uncertain, but infection is thought to occur by the oral route. Transmission can be attributable to ingestion of either sporulated oocysts from contaminated soil, food, or water or bradyzoites from undercooked meat. During acute feline infection, a cat may excrete as many as 100 million parasites per day. These very stable sporozoite-containing oocysts are highly infectious and may remain viable for many years in soil or water. Humans infected during a well-documented outbreak of oocyst-transmitted infection develop stage-specific antibodies to the oocyst/sporozoite.
Children and adults also can acquire infection from tissue cysts containing bradyzoites. The ingestion of a single cyst is all that is required for human infection. Undercooking or insufficient freezing of meat is an important source of infection in the developed world. In the United States, lamb products and pork products may show evidence of cysts that contain bradyzoites, but the overall prevalence of T. gondii has been gradually decreasing. The incidence in beef is much lower—perhaps as low as 1%. Direct ingestion of bradyzoite cysts in these various meat products leads to acute infection.